The present invention relates to a novel process for the preparation of heterocyclic compounds which are suitable as intermediates for the preparation of D-(+)-biotin, and to a process for the preparation of D-(+)-biotin itself. The invention further relates to novel intermediates in this process.
D-(+)-biotin is a substance which has been known for a long time, and there are therefore already a number of processes known for its preparation. Common to the processes of industrial interest is the necessity of adding the carboxybutyl side chain to the ring system at some stage. Various solutions are known for this, such as, for example, the synthesis of the side chain according to the scheme of linkage C.sub.4 +C.sub.1 .fwdarw.C.sub.5 or alternative (C.sub.3 +C.sub.3 -C.sub.1 =C.sub.2).fwdarw.C.sub.5 (for example, Swiss Patent 556,867).
It is also known to link the side chain with the ring system in one step by means of a Wittig reaction (for example EP-A-0 084 377). However, all these processes have the disadvantage that they either proceed via a comparatively large number of reaction steps or else require a relatively large outlay to isolate the desired final product.
The introduction of the side chain by reaction of the thiolactone of the formula I with 4-(2,4,10-trioxaadamantyl)butylmagnesium bromide is additionally known from EP-A-0 154 225.
However, this process has various disadvantages which make it appear unsuitable in the case of industrial implementation.
The cis-1,3,5-cyclohexanetriol needed for the preparation of the Grignard reagent is only poorly accessible and must be recovered again by technically complicated isolation techniques after reaction has taken place. Moreover, the yields in this process are not adequate for industrial utilization.